An attenuated insulin secretory response to glucose is characteristic of the diabetic syndrome and fetal and anolian beta cells. Some experimental evidence suggests a similar underlying mechanism for the deficient insulin secretion observed in diabetes and in the fetal pancreas. This project is concerned with obtaining a better understanding of fetal beta cells during differentiation and characterizing factors which modify the developmental course of the beta cells. Our data on the secretory dynamics of the fetal rat beta cell suggest that the first (early) phase of insulin secretion is temporally separated from the composite of both phases of insulin release. The kinetics of insulin secretion during differentiation of the fetal rat pancreas in the course of normal development and during continuous perifusion-tissue culture are being more fully characterized. The effects of various concentrations of glucose on the differentiation, replication, and maintenance of fetal beta cells during continuous perifusion-tissue culture are being determined. We are examining the role of noncarbohydrate substrates in the differentiation of fetal rat pancreas. Adult anoles (Anolis carolinensis) are hyperglycemic and their beta cells exhibit attenuated insulin release in response to glucose. Thus, the anole provides an opportunity to explore the evolution of beta cell function which is known to result utlimately in an insulin secretory deficit. Post-oviposition eggs of the anole are incubated for 18-35 days and the pancreatic rudiments of embryos are analyzed in terms of the storage and secretion of insulin. The optimal developmental stage for initiating continuous perifusion-tissue culture of anolian splenic pancreas is being determined.